It has been discovered that polarized inert noble gases can produce improved MRI images of certain areas and regions of the body that have heretofore produced less than satisfactory images in this modality. Polarized helium-3 (“3He”) and xenon-129 (“129 Xe”) have been found to be particularly suited for this purpose. Unfortunately, as will be discussed further below, the polarized state of the gases is sensitive to handling and environmental conditions and can, undesirably, decay from the polarized state relatively quickly.
Hyperpolarizers are used to produce and accumulate polarized noble gases. Hyperpolarizes artificially enhance the polarization of certain noble gas nuclei (such as 129Xe or 3He) over the natural or equilibrium levels, i.e., the Boltzmann polarization. Such an increase is desirable because it enhances and increases the MRI signal intensity, allowing physicians to obtain better images or signals of the substance in the body. See U.S. Pat. Nos. 5,545,396; 5,642,625; 5,809,801; 6,079,213, and 6,295,834; the disclosures of these patents are hereby incorporated by reference herein as if recited in full herein.
In order to produce the hyperpolarized gas, the noble gas can be blended with optically pumped alkali metal vapors such as rubidium (“Rb”). These optically pumped metal vapors collide with the nuclei of the noble gas and hyperpolarize the noble gas through a phenomenon known as “spin-exchange.” The “optical pumping” of the alkali metal vapor is produced by irradiating the alkali-metal vapor with circularly polarized light at the wavelength of the first principal resonance for the alkali metal (e.g., 795 nm for Rb). Generally stated, the ground state atoms become excited, then subsequently decay back to the ground state. Under a modest magnetic field (about 10 Gauss), the cycling of atoms between the ground and excited states can yield nearly 100% polarization of the atoms in a few microseconds. This polarization is generally carried by the lone valence electron characteristics of the alkali metal. In the presence of non-zero nuclear spin noble gases, the alkali-metal vapor atoms can collide with the noble gas atoms in a manner in which the polarization of the valence electrons is transferred to the noble-gas nuclei through a mutual spin flip “spin-exchange.”
The alkali metal is removed from the hyperpolarized gas prior to introduction into a patient to form a non-toxic and/or sterile composition. Other polarization techniques not employing alkali metal spin exchange can also be employed as is known to those of skill in the art.
Unfortunately, the hyperpolarized state of the gas can deteriorate or decay relatively quickly and therefore must be handled, collected, transported, and stored carefully. The “T1” decay constant associated with the hyperpolarized gas' longitudinal relaxation time is often used to describe the length of time it takes a gas sample to depolarize in a given situation. The handling of the hyperpolarized gas is critical because of the sensitivity of the hyperpolarized state to environmental and handling factors and the potential for undesirable decay of the gas from its hyperpolarized state prior to the planned end use, i.e., delivery to a patient for imaging. Processing, transporting, and storing the hyperpolarized gases—as well as delivery of the gas to the patient or end user—can expose the hyperpolarized gases to various relaxation mechanisms such as magnetic gradients, contact-induced relaxation, paramagnetic impurities, and the like.
At the time of dispensing the patient dose or bolus (or other point in the production cycle), the quantity of gas actually dispensed into the dose container or bag, the amount of buffer gas or supplemental gas or other fluid desired in the patient formulation of the hyperpolarized gas product, and the polarization level of the hyperpolarized gas itself can vary dose to dose. Therefore, it can be problematic, especially when blending hyperpolarized gas with a buffer gas, to provide reliable repeatable concentrations, quantities, or adjustable hyperpolarized blends of the hyperpolarized gas or gas mixtures over a plurality of doses. In addition, it may be desirable to use different amounts of gas or gas mixtures as well as different sized dose containers, patient to patient.
For example, it may be beneficial to provide different known concentrations of hyperpolarized gases (25%, 50%, and the like) within a relatively constant overall volume of inhalable gas mixture, such as a 1 or 1.5 liter volume (the remainder of the mixture being formed by suitable buffer gases). In other applications, it may be desirable to decide the appropriate formulation in situ, based on the intended use and/or polarization level of the hyperpolarized gas or fluid being dispensed.
Accordingly, there remains a need to provide improved dispensing systems to provide adjustable and/or more reliable concentrations and/or dosages of hyperpolarized gas.